TWI262919B - Naphthyridine derivative - Google Patents

Naphthyridine derivative Download PDF

Info

Publication number: TWI262919B
Authority: TW; Taiwan
Prior art keywords: ethyl; methyl; group; chlorophenyl; compound
Prior art date: 1999-10-25

Application number

TW089122260A

Other languages

English (en)

Chinese (zh)

Inventor

Masahiro Iwata

Noriyuki Kawano

Tomofumi Takuwa

Ryota Shiraki

Miki Kobayashi

Original Assignee

Yamanouchi Pharma Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-10-25

Filing date

2000-10-23

Publication date

2006-10-01

2000-10-23 Application filed by Yamanouchi Pharma Co Ltd filed Critical Yamanouchi Pharma Co Ltd

2006-10-01 Application granted granted Critical

2006-10-01 Publication of TWI262919B publication Critical patent/TWI262919B/zh

Links

150000005054 naphthyridines Chemical class 0.000 title claims description 10
150000003839 salts Chemical class 0.000 claims abstract description 28
-1 3-(4-cyclohexyl-1-ethyl-7-methyl —2 —carbonyl-1,2-dihydro-1,8-naphthyridin-3-yl)propionic acid Chemical compound 0.000 claims description 15
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 10
230000002079 cooperative effect Effects 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
235000019260 propionic acid Nutrition 0.000 claims description 5
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 5
150000003536 tetrazoles Chemical class 0.000 claims description 3
229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims 2
PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims 1
UVBBXHDRJXIQCH-UHFFFAOYSA-N 7-methyl-1h-1,8-naphthyridin-2-one Chemical compound C1=CC(=O)NC2=NC(C)=CC=C21 UVBBXHDRJXIQCH-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
KIPPZKZTINZTIR-UHFFFAOYSA-N piperidine-1,2,2,3-tetracarboxylic acid Chemical compound N1(C(C(CCC1)C(=O)O)(C(=O)O)C(=O)O)C(=O)O KIPPZKZTINZTIR-UHFFFAOYSA-N 0.000 claims 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
239000003814 drug Substances 0.000 abstract description 12
229940079593 drug Drugs 0.000 abstract description 9
125000001424 substituent group Chemical group 0.000 abstract description 9
230000003449 preventive effect Effects 0.000 abstract description 3
208000023504 respiratory system disease Diseases 0.000 abstract description 3
229940124597 therapeutic agent Drugs 0.000 abstract description 2
ZFRUGZMCGCYBRC-UHFFFAOYSA-N 1h-1,8-naphthyridin-2-one Chemical class C1=CC=NC2=NC(O)=CC=C21 ZFRUGZMCGCYBRC-UHFFFAOYSA-N 0.000 abstract 1
150000001875 compounds Chemical class 0.000 description 70
238000006243 chemical reaction Methods 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
239000000243 solution Substances 0.000 description 37
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
238000000034 method Methods 0.000 description 30
239000002904 solvent Substances 0.000 description 23
239000000203 mixture Substances 0.000 description 22
238000012360 testing method Methods 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
230000000694 effects Effects 0.000 description 12
238000010438 heat treatment Methods 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
125000000217 alkyl group Chemical group 0.000 description 9
238000001816 cooling Methods 0.000 description 8
239000000126 substance Substances 0.000 description 8
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 7
208000006673 asthma Diseases 0.000 description 7
125000000623 heterocyclic group Chemical group 0.000 description 7
238000007639 printing Methods 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
239000013078 crystal Substances 0.000 description 6
239000007788 liquid Substances 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
235000011054 acetic acid Nutrition 0.000 description 5
239000002253 acid Substances 0.000 description 5
101150117004 atg18 gene Proteins 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
229910052740 iodine Inorganic materials 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
108090000623 proteins and genes Proteins 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000000725 suspension Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 4
239000000654 additive Substances 0.000 description 4
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
125000000753 cycloalkyl group Chemical group 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
150000008282 halocarbons Chemical group 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
210000001853 liver microsome Anatomy 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
239000000047 product Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000007787 solid Substances 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 3
238000003556 assay Methods 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000008602 contraction Effects 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000008187 granular material Substances 0.000 description 3
125000001183 hydrocarbyl group Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000002503 metabolic effect Effects 0.000 description 3
229910052751 metal Chemical class 0.000 description 3
239000002184 metal Chemical class 0.000 description 3
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000008363 phosphate buffer Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000008213 purified water Substances 0.000 description 3
238000007670 refining Methods 0.000 description 3
238000010898 silica gel chromatography Methods 0.000 description 3
239000008247 solid mixture Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
210000005090 tracheal smooth muscle Anatomy 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
238000005406 washing Methods 0.000 description 3
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical class NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
206010002091 Anaesthesia Diseases 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
239000002126 C01EB10 - Adenosine Substances 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical class CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical class CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
108090000978 Interleukin-4 Proteins 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical class NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
206010057190 Respiratory tract infections Diseases 0.000 description 2
206010040070 Septic Shock Diseases 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
229960005305 adenosine Drugs 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
208000026935 allergic disease Diseases 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical class [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
230000037005 anaesthesia Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000003125 aqueous solvent Substances 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
102000023732 binding proteins Human genes 0.000 description 2
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125000004432 carbon atom Chemical group C* 0.000 description 2
YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
UQHKFADEQIVWID-UHFFFAOYSA-N cytokinin Natural products C1=NC=2C(NCC=C(CO)C)=NC=NC=2N1C1CC(O)C(CO)O1 UQHKFADEQIVWID-UHFFFAOYSA-N 0.000 description 2
239000004062 cytokinin Substances 0.000 description 2
230000018044 dehydration Effects 0.000 description 2
238000006297 dehydration reaction Methods 0.000 description 2
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
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ZUPDNLCLXSWMAE-UHFFFAOYSA-N potassium;butan-2-olate Chemical compound [K+].CCC(C)[O-] ZUPDNLCLXSWMAE-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pulmonology (AREA)
Bioinformatics & Cheminformatics (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

TW089122260A 1999-10-25 2000-10-23 Naphthyridine derivative TWI262919B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP30254499		1999-10-25

Publications (1)

Publication Number	Publication Date
TWI262919B true TWI262919B (en)	2006-10-01

Family

ID=17910254

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW089122260A TWI262919B (en)	1999-10-25	2000-10-23	Naphthyridine derivative

Country Status (16)

Country	Link
US (1)	US6740662B1 (de)
EP (1)	EP1225173B1 (de)
KR (1)	KR100699395B1 (de)
CN (1)	CN1148369C (de)
AR (1)	AR029185A1 (de)
AT (1)	ATE305470T1 (de)
AU (1)	AU779081B2 (de)
BR (1)	BR0014981A (de)
CA (1)	CA2385178A1 (de)
DE (1)	DE60022893T2 (de)
ES (1)	ES2250200T3 (de)
MX (1)	MXPA02004122A (de)
PL (1)	PL354600A1 (de)
RU (1)	RU2240322C2 (de)
TW (1)	TWI262919B (de)
WO (1)	WO2001030779A1 (de)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1487794A1 (de) *	2002-03-14	2004-12-22	Bayer Aktiengesellschaft	Monozyklische aroylpyridinone als entzündungshemmende agentien
IS7839A (is) *	2002-11-22	2004-05-23	Merck Frosst Canada Ltd.	4-oxó-1-(3-setið fenýl-1,4-díhýdró-1,8-naftýridín-3-karboxamíð fosfódíesterasa-4 hindrar
EP1660087A2 (de) *	2003-07-22	2006-05-31	Janssen Pharmaceutica N.V.	Chinolinon-derivate als c-fms-kinase-hemmer
PT1685849E (pt) *	2003-11-20	2012-02-15	Astellas Pharma Inc	Inibidores de pde4 para o tratamento da cistite intersticial
TW200726767A (en) *	2005-07-04	2007-07-16	Astrazeneca Ab	Chemical compounds 2
EP2258358A3 (de)	2005-08-26	2011-09-07	Braincells, Inc.	Neurogenese mit Acetylcholinesterasehemmer
EP2275095A3 (de)	2005-08-26	2011-08-17	Braincells, Inc.	Neurogenese durch modulation des Muscarinrezeptors
EP1940389A2 (de)	2005-10-21	2008-07-09	Braincells, Inc.	Modulation von neurogenese durch pde-hemmung
AU2006308889A1 (en)	2005-10-31	2007-05-10	Braincells, Inc.	GABA receptor mediated modulation of neurogenesis
AU2007218725B2 (en) *	2006-02-21	2011-12-01	Eisai R & D Management Co., Ltd.	4-(3-benzoylaminophenyl)-6,7-dimethoxy-2- methylaminoquinazoline derivative
US20100216734A1 (en)	2006-03-08	2010-08-26	Braincells, Inc.	Modulation of neurogenesis by nootropic agents
EP2382975A3 (de)	2006-05-09	2012-02-29	Braincells, Inc.	Neurogenese mittels Angiotensin-Modulation
JP2009536667A (ja)	2006-05-09	2009-10-15	ブレインセルス，インコーポレイティド	５ｈｔ受容体介在性の神経新生
JP5440934B2 (ja)	2006-05-24	2014-03-12	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	置換プテリジン
AU2007292848A1 (en)	2006-09-08	2008-03-13	Braincells, Inc.	Combinations containing a 4-acylaminopyridine derivative
US20100184806A1 (en)	2006-09-19	2010-07-22	Braincells, Inc.	Modulation of neurogenesis by ppar agents
WO2008071964A1 (en) *	2006-12-15	2008-06-19	Astrazeneca Ab	Naphthyridine bactericides
US8530654B2 (en) *	2007-02-16	2013-09-10	Eisai R&D Management Co., Ltd.	Crystals, amorphous substances or salts of methyl N-[3-(6,7-dimethoxy-2-methylaminoquinazolin-4-yl) phenyl] terephthalamic acid
CA2696793A1 (en)	2007-08-17	2009-02-26	Eisai R&D Management Co., Ltd.	Novel preparation for external use
AU2008290000B2 (en) *	2007-08-17	2012-05-10	Eisai R & D Management Co., Ltd.	Method for producing quinazoline derivative
WO2009088054A1 (ja)	2008-01-11	2009-07-16	Astellas Pharma Inc.	精巣の疼痛又は不快感行動及び頻尿併発モデル動物
AU2009314760B2 (en) *	2008-11-11	2011-11-10	Je Il Pharmaceutical Co.,Ltd	Novel tricyclic derivative or pharmaceutically acceptable salts thereof, preparation method thereof, and pharmaceutical composition containing the same
WO2010099217A1 (en)	2009-02-25	2010-09-02	Braincells, Inc.	Modulation of neurogenesis using d-cycloserine combinations
US10731199B2 (en) *	2011-11-21	2020-08-04	Advanced Liquid Logic, Inc.	Glucose-6-phosphate dehydrogenase assays
WO2013106547A1 (en)	2012-01-10	2013-07-18	President And Fellows Of Harvard College	Beta-cell replication promoting compounds and methods of their use
AU2018340475B2 (en) *	2017-09-28	2023-01-19	Transthera Sciences (Nanjing), Inc.	PDE9 inhibitor and use thereof
CN111471059B (zh) *	2019-01-23	2022-12-02	药捷安康(南京)科技股份有限公司	Pde9抑制剂及其用途
WO2020182076A1 (zh) *	2019-03-08	2020-09-17	南京药捷安康生物科技有限公司	磷酸二酯酶抑制剂的用途
KR102779311B1 (ko) *	2019-03-15	2025-03-11	트렌스테라 사이언스즈 (난징), 인코포레이티드	포스포디에스테라제 억제제의 결정형, 이의 제조 방법 및 이의 용도

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4324893A (en)	1979-04-18	1982-04-13	American Home Products Corporation	4-Amino-3-carboxy or cyano-1,2-dihydro-2-oxo-1,8-naphthyridine derivatives
JPS55164682A (en) *	1979-06-11	1980-12-22	Yamanouchi Pharmaceut Co Ltd	1-alkyl-2-oxo-2h-1,8-naphthyridine derivative and its preparation
EP0267691A3 (de) *	1986-10-15	1989-08-23	Schering Corporation	Verwendung von 1-substituierten Naphthyridin- und Pyridopyrazinderivaten für die Herstellung von Immunosuppressoren-arzneimittel.
AU664912B2 (en) *	1992-09-02	1995-12-07	Dainippon Pharmaceutical Co. Ltd.	Novel 3-oxadiazolyl-1,6-naphthyridine derivatives
WO1994012499A1 (fr) *	1992-12-01	1994-06-09	The Green Cross Corporation	Derive de 1,8-naphthyridin-2-one et utilisation de ce derive
JPH0710875A (ja) *	1993-06-21	1995-01-13	Green Cross Corp:The	選択的ホスホジエステラーゼｉｖ阻害剤
JPH07126268A (ja) *	1993-10-29	1995-05-16	Otsuka Pharmaceut Factory Inc	１，８−ナフチリジン誘導体
WO1996006843A1 (en) *	1994-08-29	1996-03-07	Yamanouchi Pharmaceutical Co., Ltd.	Novel naphthyridine derivative and medicinal composition thereof
DE69633059T2 (de)	1995-05-31	2005-08-18	Sumitomo Pharmaceuticals Co., Ltd.	Neue naphthyridinderivate.
NZ335766A (en)	1996-11-26	2000-11-24	Sumitomo Pharma	Naphthyridine derivatives and use as acyl-CoA cholesterol acyl transferase(ACAT) inhibitor as treatment of hyperlipidemia
WO1999043659A1 (en) *	1998-02-25	1999-09-02	Sumitomo Pharmaceuticals Co., Ltd.	Pyridone derivatives and process for producing the same

2000
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- 2000-10-23 AR ARP000105559A patent/AR029185A1/es active IP Right Grant
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Also Published As

Publication number	Publication date
EP1225173B1 (de)	2005-09-28
EP1225173A1 (de)	2002-07-24
CA2385178A1 (en)	2001-05-03
CN1148369C (zh)	2004-05-05
US6740662B1 (en)	2004-05-25
AU779081B2 (en)	2005-01-06
KR100699395B1 (ko)	2007-03-27
CN1382141A (zh)	2002-11-27
MXPA02004122A (es)	2003-02-12
DE60022893T2 (de)	2006-07-13
ATE305470T1 (de)	2005-10-15
KR20020041477A (ko)	2002-06-01
WO2001030779A1 (en)	2001-05-03
AR029185A1 (es)	2003-06-18
PL354600A1 (en)	2004-01-26
BR0014981A (pt)	2002-07-16
DE60022893D1 (de)	2006-02-09
AU7956000A (en)	2001-05-08
RU2240322C2 (ru)	2004-11-20
EP1225173A4 (de)	2003-08-20
ES2250200T3 (es)	2006-04-16

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2009-07-11	MM4A	Annulment or lapse of patent due to non-payment of fees

Publication	Publication Date	Title
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